帕博利珠单抗单药治疗 PD-L1 阳性晚期非小细胞肺癌老年患者的安全性和有效性：来自 KEYNOTE-010、KEYNOTE-024 和 KEYNOTE-042 研究的汇总分析。
Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies.
机构信息
National Hospital Organization Kyushu Cancer Center, Minami-ku, Fukuoka-shi, Fukuoka 811-1395, Japan.
National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi 460-0001, Japan.
出版信息
Lung Cancer. 2019 Sep;135:188-195. doi: 10.1016/j.lungcan.2019.07.004. Epub 2019 Jul 8.
OBJECTIVES
Most lung cancer diagnoses occur in elderly patients, who are underrepresented in clinical trials. We present a pooled analysis of safety and efficacy in elderly patients (≥75 years) who received pembrolizumab (a programmed death 1 inhibitor) for advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1)‒positive tumors.
METHODS
The pooled analysis included patients aged ≥18 years with advanced NSCLC with PD-L1-positive tumors from the KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) studies. In KEYNOTE-010, patients were randomized to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel, as second- or later-line therapy. In KEYNOTE-024 and KEYNOTE-042, patients were randomized to first-line pembrolizumab 200 mg Q3W or platinum-based chemotherapy. Overall survival (OS) was estimated by the Kaplan-Meier method, and safety data were summarized in elderly patients (≥75 years).
RESULTS
The analysis included 264 elderly patients with PD-L1-positive tumors (PD-L1 tumor proportion score [TPS] ≥1%); among these, 132 had PD-L1 TPS ≥ 50%. Pembrolizumab improved OS among elderly patients with PD-L1 TPS ≥ 1% (hazard ratio [HR], 0.76 [95% CI, 0.56-1.02]) and PD-L1 TPS ≥ 50% (HR, 0.40 [95% CI, 0.25-0.64]). Pembrolizumab as first-line therapy also improved OS among elderly patients with PD-L1 TPS ≥ 50% (from KEYNOTE-024 and KEYNOTE-042) compared with chemotherapy (HR, 0.41 [95% CI, 0.23‒0.73]). Pembrolizumab was associated with fewer treatment-related adverse events (AEs) in elderly patients (overall, 68.5% vs 94.3%; grade ≥3, 24.2% vs 61.0%) versus chemotherapy. Immune-mediated AEs and infusion reactions were more common with pembrolizumab versus chemotherapy (overall, 24.8% vs 6.7%; grade 3‒4: 9.4% vs 0%; no grade 5 events).
CONCLUSIONS
In this pooled analysis of elderly patients with advanced NSCLC with PD-L1‒positive tumors, pembrolizumab improved OS versus chemotherapy, with a more favorable safety profile. Outcomes with pembrolizumab in patients ≥75 years were comparable to those in the overall populations in the individual studies.
目的
大多数肺癌诊断发生在老年患者中，而临床试验中代表性不足。我们报告了一项对接受 pembrolizumab（程序性死亡 1 抑制剂）治疗的晚期非小细胞肺癌（NSCLC）老年患者（≥75 岁）的安全性和疗效的汇总分析，这些患者的肿瘤 PD-L1 阳性。
方法
汇总分析纳入了来自 KEYNOTE-010（NCT01905657）、KEYNOTE-024（NCT02142738）和 KEYNOTE-042（NCT02220894）研究中年龄≥18 岁、PD-L1 阳性肿瘤的晚期 NSCLC 患者。在 KEYNOTE-010 中，患者被随机分配接受 pembrolizumab 2 或 10mg/kg，每 3 周（Q3W）或多西他赛作为二线或后续治疗。在 KEYNOTE-024 和 KEYNOTE-042 中，患者被随机分配接受一线 pembrolizumab 200mg Q3W 或铂类化疗。总生存期（OS）通过 Kaplan-Meier 方法估计，安全性数据在老年患者（≥75 岁）中进行了总结。
结果
该分析包括 264 名 PD-L1 阳性肿瘤的老年患者（PD-L1 肿瘤比例评分 [TPS]≥1%）；其中，132 名患者的 PD-L1 TPS≥50%。Pembrolizumab 改善了 PD-L1 TPS≥1%（风险比 [HR]，0.76 [95%CI，0.56-1.02]）和 PD-L1 TPS≥50%（HR，0.40 [95%CI，0.25-0.64]）的老年患者的 OS。Pembrolizumab 作为一线治疗也改善了 PD-L1 TPS≥50%的老年患者（来自 KEYNOTE-024 和 KEYNOTE-042）的 OS 与化疗（HR，0.41 [95%CI，0.23-0.73]）。与化疗相比，pembrolizumab 在老年患者中与较少的治疗相关不良事件（AE）相关（总体而言，68.5% vs 94.3%；≥3 级，24.2% vs 61.0%）。与化疗相比，免疫介导的 AE 和输注反应在 pembrolizumab 中更为常见（总体而言，24.8% vs 6.7%；3-4 级：9.4% vs 0%；无 5 级事件）。
结论
在这项对 PD-L1 阳性肿瘤的晚期 NSCLC 老年患者的汇总分析中，与化疗相比，pembrolizumab 改善了 OS，且安全性更好。≥75 岁患者的 pembrolizumab 治疗结果与各研究中的总体人群相当。
Zotero 插件